Factors Modulating Parameters of Cholesterol Homeostasis in the Metabolic Syndrome

Overview

Background.
Newly described component of the metabolic syndrome is the elevated synthesis of cholesterol accompanied with its decreased intestinal absorption. The aim of our study was to ascertain the incidence of genotypes and alleles of several candidate genes, which modulate insulin resistance and metabolism of lipids and to find their role in lipid, lipoprotein and cholesterol homeostasis. The concentrations of cholesterol precursors (lathosterol, desmosterol, respectively their rations to cholesterol) are related to the synthesis of cholesterol; concentrations of fytosterols (kampesterol, sitosterol, respectively their rations to cholesterol) are related to the intestinal absorption of cholesterol.

Methods and Results.
95 patients with metabolic syndrome (56 M/39 F) and 195 healthy persons (99 M/96 F) were included into the study. Beside the basic clinical and anthropometric data, parameters of glucose homeostasis, plasma concentration of lipids, ultracentrifugation separated lipoproteins, and conjugated diens in LDL were determined. Non-cholesterol sterols were estimated by capillary gas chromatography. Polymorphisms of apolipoprotein E, intestinal isoforms of fatty acids binding protein (Ala54Thr), microsomal transfer protein (–493G/T), and γ-2 isoforms of peroxisomal proliferator activated receptor (Ala12Pro) were analysed by combination of methods of polymerase chain reaction and by determination of polymorphism of the length of restriction fragments. After adjustation to the age, patients with metabolic syndrome had higher BMI, body fat and lean body weight (all P<0.001), waist circumference, systolic and diastolic blood pressure (all P<0.01). At the same time they had higher levels of glucose, insulin (P<0.001), C-peptide, CRP (P<0.05), uric acid, conjugated diens in LDL and HOMA insulin resistance index (P<0.001). After adjustation to the age, higher concentration of triglycerides (P<0.001), apo B (P<0.01), cholesterol and triglycerides in VLDL (both P<0.001), triglycerides in LDL (P<0.01) were found. Incidence of alleles and genotypes of studied polymorphisms did not differ in both groups. Cholesterol synthesis is modulated by the presence of metabolic syndrome and by sex; cholesterol resorption is modulated only by the presence of metabolic syndrome.

Conclusions.
In patients with metabolic syndrome we found higher synthesis and lower intestinal absorption of cholesterol. We did not confirm relation between alleles of studied polymorphisms and clinical and anthropometric parameters, neither relation of these alleles to lipid or lipoprotein levels, oxidation stress, inflammation, or parameters of synthesis and absorption of cholesterol.

Key words:
metabolic syndrome, synthesis and absorption of cholesterol, cholesterol precursors and fytosterols, gene polymorphisms.